Hitomi J, Kimura T, Kusumi E, Nakagawa S, Kuwabara S, Hatakeyama K, Yamaguchi K
Department of Anatomy, Niigata University School of Medicine, Japan.
Arch Histol Cytol. 1998 May;61(2):163-78. doi: 10.1679/aohc.61.163.
CAAF1 and CAAF2, newly identified calcium-binding proteins from bovine amniotic fluid, have been revealed to be members of the S100 protein family preferentially produced by fetal squamous epithelial cells, including epidermal keratinocytes. Having previously cloned the cDNA of human CAAF1 protein from the esophageal epithelium, we report here on the characteristic expression pattern of CAAF1 and related S100 proteins in human esophageal epithelial cells. Normal cells of the human esophageal epithelium expressed CAAF1, and also expressed the homologous novel S100 proteins including CAAF2, MRP8, and MRP14, but not S100alpha. An immunohistochemical study with specific monoclonal antibodies against CAAF1 proteins demonstrated that CAAF1 proteins were produced by the esophageal epithelial cells in the process of cell differentiation. The immature proliferating cells in the epithelium did not produce CAAF1 proteins, but the differentiated cells expressed CAAF1, which overlay the immature cells and were stratifying in the epithelium. These CAA 1-producing cells did not show any proliferating activities. Esophageal carcinoma cells did not express CAAF1, except for the keratinized cells with no proliferating activity. In addition, the forced expression of CAAF1 proteins in the carcinoma cells resulted in a marked decrease in DNA synthesis. These findings indicate that human esophageal epithelial cells express the multiple genes of S100 proteins including CAAF proteins, and that CAAF1 is closely associated with the terminal differentiation of these cells. CAAF1 expression also might play some role in cell growth.
CAAF1和CAAF2是新发现的来自牛羊水的钙结合蛋白，已被证实是S100蛋白家族的成员，优先由包括表皮角质形成细胞在内的胎儿鳞状上皮细胞产生。此前我们已从食管上皮中克隆出人类CAAF1蛋白的cDNA，在此我们报告CAAF1及相关S100蛋白在人类食管上皮细胞中的特征性表达模式。人类食管上皮的正常细胞表达CAAF1，也表达包括CAAF2、MRP8和MRP14在内的同源新型S100蛋白，但不表达S100α。用针对CAAF1蛋白的特异性单克隆抗体进行的免疫组织化学研究表明，CAAF1蛋白是在细胞分化过程中由食管上皮细胞产生的。上皮中未成熟的增殖细胞不产生CAAF1蛋白，但分化细胞表达CAAF1，其覆盖在未成熟细胞之上并在上皮中分层。这些产生CAA 1的细胞没有任何增殖活性。食管癌细胞不表达CAAF1，除了没有增殖活性的角化细胞。此外，在癌细胞中强制表达CAAF1蛋白导致DNA合成显著减少。这些发现表明，人类食管上皮细胞表达包括CAAF蛋白在内的多种S100蛋白基因，并且CAAF1与这些细胞的终末分化密切相关。CAAF1的表达也可能在细胞生长中发挥某些作用。
